This is a collaborative research program jointly developed by researchers from La Jolla Institute for Allergy and Immunology and The Scripps Research Institute. The title and central theme of this program project is "Signaling in Allergic Inflammation." We propose to address basic pathophysiologic mechanisms of human asthma by examining cell-cell communication and intracellular signaling in mast cells, T cells, fibroblasts, and epithelial cells. The program is composed of four interrelated biomedical research projects that are highly relevant to allergic inflammation, and a D&E project. Project 1. Signal transduction pathways in Th2 subset (PI, Altman, Co-PI, Grey), will extensively analyze differences in the signaling mechanisms between Th1 and Th2 subset. Project 2. Role of cytoskeleton in mst cell signaling (PI, Kawakami, Co-PI, Apgar), will focus on the interaction between components involved in signaling pathways and cytoskeleton in mast cells. PROJECT 3. Regulatory role of FcepsilonRI in allergic inflammation (PI, Liu, Co-PIs Chen and Croft), will address the newly recognized regulatory role of mast cells in antigen presentation and induction of IgE synthesis. PROJECT 4, Kinins, signaling, and asthma: a novel paradigm (PI, Zuraw, Co-PI, Ye), will deal with the role of kinin receptors and signaling mechanisms through these receptors in allergic inflammation. D&E Project, Inner city asthma (PL Christiansen), will utilize the San Diego United School District for examining prevalence and severity of asthma as well as benefit of educational program in schools with a preponderance of ethnic minority and economically disadvantaged youth. In our view, allergic inflammation involves basic mechanisms, in which T cells play an important regulatory role and mast cells are one of the key effector cells. Allergic inflammation also involves amplification mechanisms provided by various cell types, cytokines and mediators. We have selected T cells and mast cells as two key cell types to be focused on by this program--Project 1 focuses on T cells and Project 2 concerns mast cells, while Project 3 deals with interactions between these two cell types. We have also selected kinins as an example of mediators involved in the amplification mechanisms of allergic inflammation, which ar the research subject of Project 4. This program has been designed to maximize collaborative efforts. All four biomedical projects represent a collaborative effort between two or three established investigators with complementary expertise. Extensive interproject interactions and collaborations will be promoted by the interrelated nature of the projects.